1479O - Efficacy/safety of palonosetron vs ondansetron in preventing chemotherapy-induced nausea and vomiting (CINV) in pediatric patients receiving modera...

Date 27 September 2014
Event ESMO 2014
Session Supportive and palliative care
Topics Supportive Care
Cancer in Special Situations
Presenter Edita Kabickova
Citation Annals of Oncology (2014) 25 (suppl_4): iv517-iv541. 10.1093/annonc/mdu356
Authors G. Kovacs1, A. Wachtel2, E. Basharova3, T. Spinelli4, P. Nicolas5, E. Kabickova6
  • 1Second Department Of Pediatrics, Semmelweis University, 1094 - Budapest/HU
  • 2Department Of Pediatrics, Instituto Nacional de Enfermedades Neoplasicas, Lima/PE
  • 3Oncohematology Center, Chelyabinsk Pediatric Regional Clinical Hospital, Chelyabinsk/RU
  • 4Statistics, Helsinn Healthcare SA, Lugano/CH
  • 5Research, Helsinn Healthcare SA, Lugano/CH
  • 6Department Of Pediatric Hematology And Oncology, Charles University 2nd Medical School, Prague/CZ

 

Abstract

Aim

Evaluate the efficacy and safety of two dose-levels of palonosetron (PALO) vs ondansetron (the standard of care comparator) in the prevention of CINV in pediatric patients receiving MEC/HEC in a multicenter, multinational, randomized, double-blind study.

Methods

Patients with malignant disease scheduled to receive MEC/HEC were randomized to receive PALO (low-dose: 10 mcg/kg, maximum dose 0.75 mg; high-dose: 20 mcg/kg, maximum dose 1.5 mg) or ondansetron (3 x 150 mcg/kg, maximum dose 32 mg). The primary objective was to demonstrate the non-inferiority of PALO (&dgr;=-15%) vs ondansetron in terms of patients with a complete response (CR: no emesis/rescue medication) in the acute phase (0–24h after chemotherapy administration). Secondary objectives included CR rate in the delayed (25–120h) and overall (0–120h) phases, safety and tolerability.

Results

A total of 502 patients were randomized and 493 included in the full analysis set (166 low-, 165 high-dose PALO; 162 ondansetron). Aged between 64 days and 16.9 years, the majority of patients were male (53.1%) and white (95.1%). The CR rate (acute phase) was 54.2% and 59.4% for low- and high-dose PALO patients, and 58.6% for ondansetron patients. Statistical analysis confirmed non-inferiority for high-dose PALO. The CR rate (delayed phase) was 28.9% and 38.8% in the low- and high-dose PALO groups, and 28.4% in the ondansetron group, with similar results in the overall phase. Treatment-emergent adverse events (TEAEs) were 80.2% and 69.3% in the low- and high-dose PALO groups, and 81.7% in the ondansetron group. The most frequently reported drug-related TEAE was headache (low-dose PALO: 1.8%; high-dose PALO: 0.6%; ondansetron: 1.2%). Three patients (1 high-dose PALO; 2 ondansetron) also experienced prolonged QTc intervals, but these events were considered to be non-serious. All withdrawals and/or deaths were unrelated to the study drug.

Conclusions

High-dose PALO is efficacious for the prevention of CINV in pediatric patients receiving MEC/HEC, and non-inferior to ondansetron as supported by statistical analyses. The safety profiles raised no concerns.

Disclosure

T. Spinelli: Tulla Spinelli is an employee of Helsinn Healthcare SA; P. Nicolas: Pierre Nicolas is an employee of Helsinn Healthcare SA. All other authors have declared no conflicts of interest.